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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial

Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial... Full description

Journal Title: The Lancet (British edition) 2011, Vol.377 (9784), p.2181-2192
Main Author: Baigent, Colin, Prof
Other Authors: Landray, Martin J, FRCP , Reith, Christina, MRCP , Emberson, Jonathan, PhD , Wheeler, David C, FRCP , Tomson, Charles, DM , Wanner, Christoph, Prof , Krane, Vera, MD , Cass, Alan, Prof , Craig, Jonathan, Prof , Neal, Bruce, Prof , Jiang, Lixin, MD , Hooi, Lai Seong, FRCP , Levin, Adeera, Prof , Agodoa, Lawrence, Prof , Gaziano, Mike, Prof , Kasiske, Bertram, Prof , Walker, Robert, Prof , Massy, Ziad A, Prof , Feldt-Rasmussen, Bo, Prof , Krairittichai, Udom, MD , Ophascharoensuk, Vuddidhej, MD , Fellström, Bengt, Prof , Holdaas, Hallvard, MD , Tesar, Vladimir, Prof , Wiecek, Andrzej, Prof , Grobbee, Diederick, Prof , de Zeeuw, Dick, Prof , Grönhagen-Riska, Carola, Prof , Dasgupta, Tanaji, MRCP , Lewis, David, MRCP , Herrington, William, MRCP , Mafham, Marion, MD , Majoni, William, FRACP , Wallendszus, Karl, MSc , Grimm, Richard, Prof , Pedersen, Terje, Prof , Tobert, Jonathan, PhD , Armitage, Jane, Prof , Baxter, Alex, BA , Bray, Christopher, PhD , Chen, Yiping, DPhil , Chen, Zhengming, Prof , Hill, Michael, DPhil , Knott, Carol, MSc , Parish, Sarah, DPhil , Simpson, David , Sleight, Peter, Prof , Young, Alan, DPhil , Collins, Rory, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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recordid: cdi_swepub_primary_oai_DiVA_org_uu_156228
title: The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
format: Article
creator:
  • Baigent, Colin, Prof
  • Landray, Martin J, FRCP
  • Reith, Christina, MRCP
  • Emberson, Jonathan, PhD
  • Wheeler, David C, FRCP
  • Tomson, Charles, DM
  • Wanner, Christoph, Prof
  • Krane, Vera, MD
  • Cass, Alan, Prof
  • Craig, Jonathan, Prof
  • Neal, Bruce, Prof
  • Jiang, Lixin, MD
  • Hooi, Lai Seong, FRCP
  • Levin, Adeera, Prof
  • Agodoa, Lawrence, Prof
  • Gaziano, Mike, Prof
  • Kasiske, Bertram, Prof
  • Walker, Robert, Prof
  • Massy, Ziad A, Prof
  • Feldt-Rasmussen, Bo, Prof
  • Krairittichai, Udom, MD
  • Ophascharoensuk, Vuddidhej, MD
  • Fellström, Bengt, Prof
  • Holdaas, Hallvard, MD
  • Tesar, Vladimir, Prof
  • Wiecek, Andrzej, Prof
  • Grobbee, Diederick, Prof
  • de Zeeuw, Dick, Prof
  • Grönhagen-Riska, Carola, Prof
  • Dasgupta, Tanaji, MRCP
  • Lewis, David, MRCP
  • Herrington, William, MRCP
  • Mafham, Marion, MD
  • Majoni, William, FRACP
  • Wallendszus, Karl, MSc
  • Grimm, Richard, Prof
  • Pedersen, Terje, Prof
  • Tobert, Jonathan, PhD
  • Armitage, Jane, Prof
  • Baxter, Alex, BA
  • Bray, Christopher, PhD
  • Chen, Yiping, DPhil
  • Chen, Zhengming, Prof
  • Hill, Michael, DPhil
  • Knott, Carol, MSc
  • Parish, Sarah, DPhil
  • Simpson, David
  • Sleight, Peter, Prof
  • Young, Alan, DPhil
  • Collins, Rory, Prof
subjects:
  • Adult
  • Aged
  • Azetidines
  • Azetidines - administration & dosage
  • Basic Medicine
  • Biological and medical sciences
  • Blind Method
  • Cardiovascular Diseases
  • Cardiovascular Diseases - prevention & control
  • CARDIOVASCULAR EVENTS
  • Cholesterol
  • Cholesterol, LDL - analysis
  • Cholesterol, LDL - drug effects
  • Chronic
  • Combination
  • Confidence Intervals
  • DESIGN
  • Diagnosis
  • Dose
  • Dose-Response Relationship, Drug
  • Double
  • Double-Blind Method
  • Drug
  • Drug Administration Schedule
  • Drug Therapy
  • Drug Therapy, Combination
  • EFFICACY
  • Ezetimibe
  • Farmaceutiska vetenskaper
  • FARMACI
  • Fast track
  • Fast track — Articles
  • Female
  • Follow
  • Follow-Up Studies
  • General aspects
  • Health aspects
  • HEMODIALYSIS
  • Humans
  • Hypolipidemic Agents
  • Hypolipidemic Agents - administration & dosage
  • Hypolipidemic Agents - adverse effects
  • Internal Medicine
  • Kidney diseases
  • Kidney Function Tests
  • Kidneys
  • Low density lipoproteins
  • Male
  • Medical and Health Sciences
  • Medical sciences
  • Medicin och hälsovetenskap
  • Medicinska och farmaceutiska grundvetenskaper
  • METAANALYSIS
  • Middle Aged
  • Nephrology. Urinary tract diseases
  • Nephropathies. Renovascular diseases. Renal failure
  • OUTCOMES
  • PARTICIPANTS
  • Pharmaceutical Sciences
  • PHARMACY
  • Physiological aspects
  • Reference Values
  • Renal Dialysis
  • Renal Dialysis - methods
  • Renal Dialysis - mortality
  • Renal failure
  • Renal Insufficiency
  • Renal Insufficiency, Chronic - diagnosis
  • Renal Insufficiency, Chronic - drug therapy
  • Renal Insufficiency, Chronic - mortality
  • Renal Insufficiency, Chronic - therapy
  • REQUIRING PROLONGED OBSERVATION
  • Research
  • Response Relationship
  • Risk Assessment
  • SAFETY
  • Severity of Illness Index
  • Simvastatin
  • Simvastatin - administration & dosage
  • Simvastatin - adverse effects
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • UMCG Approved
  • UNITED-KINGDOM HEART
  • Up Studies
  • Urinary system involvement in other diseases. Miscellaneous
ispartof: The Lancet (British edition), 2011, Vol.377 (9784), p.2181-2192
description: Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
  • 1474-547X
url: Link


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titleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
sourceAlma/SFX Local Collection
creatorBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof
creatorcontribBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof ; on behalf of the SHARP Investigators ; SHARP Investigators
descriptionSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
identifier
0ISSN: 0140-6736
1ISSN: 1474-547X
2EISSN: 1474-547X
3DOI: 10.1016/S0140-6736(11)60739-3
4PMID: 21663949
5CODEN: LANCAO
languageeng
publisherKidlington: Elsevier Ltd
subjectAdult ; Aged ; Azetidines ; Azetidines - administration & dosage ; Basic Medicine ; Biological and medical sciences ; Blind Method ; Cardiovascular Diseases ; Cardiovascular Diseases - prevention & control ; CARDIOVASCULAR EVENTS ; Cholesterol ; Cholesterol, LDL - analysis ; Cholesterol, LDL - drug effects ; Chronic ; Combination ; Confidence Intervals ; DESIGN ; Diagnosis ; Dose ; Dose-Response Relationship, Drug ; Double ; Double-Blind Method ; Drug ; Drug Administration Schedule ; Drug Therapy ; Drug Therapy, Combination ; EFFICACY ; Ezetimibe ; Farmaceutiska vetenskaper ; FARMACI ; Fast track ; Fast track — Articles ; Female ; Follow ; Follow-Up Studies ; General aspects ; Health aspects ; HEMODIALYSIS ; Humans ; Hypolipidemic Agents ; Hypolipidemic Agents - administration & dosage ; Hypolipidemic Agents - adverse effects ; Internal Medicine ; Kidney diseases ; Kidney Function Tests ; Kidneys ; Low density lipoproteins ; Male ; Medical and Health Sciences ; Medical sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; METAANALYSIS ; Middle Aged ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; OUTCOMES ; PARTICIPANTS ; Pharmaceutical Sciences ; PHARMACY ; Physiological aspects ; Reference Values ; Renal Dialysis ; Renal Dialysis - methods ; Renal Dialysis - mortality ; Renal failure ; Renal Insufficiency ; Renal Insufficiency, Chronic - diagnosis ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - mortality ; Renal Insufficiency, Chronic - therapy ; REQUIRING PROLONGED OBSERVATION ; Research ; Response Relationship ; Risk Assessment ; SAFETY ; Severity of Illness Index ; Simvastatin ; Simvastatin - administration & dosage ; Simvastatin - adverse effects ; Survival Analysis ; Time Factors ; Treatment Outcome ; UMCG Approved ; UNITED-KINGDOM HEART ; Up Studies ; Urinary system involvement in other diseases. Miscellaneous
ispartofThe Lancet (British edition), 2011, Vol.377 (9784), p.2181-2192
rights
0Elsevier Ltd
12011 Elsevier Ltd
2info:eu-repo/semantics/restrictedAccess
32015 INIST-CNRS
4Copyright © 2011 Elsevier Ltd. All rights reserved.
5COPYRIGHT 2011 Elsevier B.V.
62011 Elsevier Ltd. All rights reserved. 2011 Elsevier Ltd
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1942t-2c4cacf2dad59e78577d3d7f8f58c935f8a8c2afdd8add5811d56c439c2b7e6d3
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creatorcontrib
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
50on behalf of the SHARP Investigators
51SHARP Investigators
title
0The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
1The Lancet (British edition)
addtitleLancet
descriptionSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
subject
0Adult
1Aged
2Azetidines
3Azetidines - administration & dosage
4Basic Medicine
5Biological and medical sciences
6Blind Method
7Cardiovascular Diseases
8Cardiovascular Diseases - prevention & control
9CARDIOVASCULAR EVENTS
10Cholesterol
11Cholesterol, LDL - analysis
12Cholesterol, LDL - drug effects
13Chronic
14Combination
15Confidence Intervals
16DESIGN
17Diagnosis
18Dose
19Dose-Response Relationship, Drug
20Double
21Double-Blind Method
22Drug
23Drug Administration Schedule
24Drug Therapy
25Drug Therapy, Combination
26EFFICACY
27Ezetimibe
28Farmaceutiska vetenskaper
29FARMACI
30Fast track
31Fast track — Articles
32Female
33Follow
34Follow-Up Studies
35General aspects
36Health aspects
37HEMODIALYSIS
38Humans
39Hypolipidemic Agents
40Hypolipidemic Agents - administration & dosage
41Hypolipidemic Agents - adverse effects
42Internal Medicine
43Kidney diseases
44Kidney Function Tests
45Kidneys
46Low density lipoproteins
47Male
48Medical and Health Sciences
49Medical sciences
50Medicin och hälsovetenskap
51Medicinska och farmaceutiska grundvetenskaper
52METAANALYSIS
53Middle Aged
54Nephrology. Urinary tract diseases
55Nephropathies. Renovascular diseases. Renal failure
56OUTCOMES
57PARTICIPANTS
58Pharmaceutical Sciences
59PHARMACY
60Physiological aspects
61Reference Values
62Renal Dialysis
63Renal Dialysis - methods
64Renal Dialysis - mortality
65Renal failure
66Renal Insufficiency
67Renal Insufficiency, Chronic - diagnosis
68Renal Insufficiency, Chronic - drug therapy
69Renal Insufficiency, Chronic - mortality
70Renal Insufficiency, Chronic - therapy
71REQUIRING PROLONGED OBSERVATION
72Research
73Response Relationship
74Risk Assessment
75SAFETY
76Severity of Illness Index
77Simvastatin
78Simvastatin - administration & dosage
79Simvastatin - adverse effects
80Survival Analysis
81Time Factors
82Treatment Outcome
83UMCG Approved
84UNITED-KINGDOM HEART
85Up Studies
86Urinary system involvement in other diseases. Miscellaneous
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startdate2011
enddate2011
creator
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
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3Lancet Publishing Group
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creationdate2011
titleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
authorBaigent, Colin, Prof ; Landray, Martin J, FRCP ; Reith, Christina, MRCP ; Emberson, Jonathan, PhD ; Wheeler, David C, FRCP ; Tomson, Charles, DM ; Wanner, Christoph, Prof ; Krane, Vera, MD ; Cass, Alan, Prof ; Craig, Jonathan, Prof ; Neal, Bruce, Prof ; Jiang, Lixin, MD ; Hooi, Lai Seong, FRCP ; Levin, Adeera, Prof ; Agodoa, Lawrence, Prof ; Gaziano, Mike, Prof ; Kasiske, Bertram, Prof ; Walker, Robert, Prof ; Massy, Ziad A, Prof ; Feldt-Rasmussen, Bo, Prof ; Krairittichai, Udom, MD ; Ophascharoensuk, Vuddidhej, MD ; Fellström, Bengt, Prof ; Holdaas, Hallvard, MD ; Tesar, Vladimir, Prof ; Wiecek, Andrzej, Prof ; Grobbee, Diederick, Prof ; de Zeeuw, Dick, Prof ; Grönhagen-Riska, Carola, Prof ; Dasgupta, Tanaji, MRCP ; Lewis, David, MRCP ; Herrington, William, MRCP ; Mafham, Marion, MD ; Majoni, William, FRACP ; Wallendszus, Karl, MSc ; Grimm, Richard, Prof ; Pedersen, Terje, Prof ; Tobert, Jonathan, PhD ; Armitage, Jane, Prof ; Baxter, Alex, BA ; Bray, Christopher, PhD ; Chen, Yiping, DPhil ; Chen, Zhengming, Prof ; Hill, Michael, DPhil ; Knott, Carol, MSc ; Parish, Sarah, DPhil ; Simpson, David ; Sleight, Peter, Prof ; Young, Alan, DPhil ; Collins, Rory, Prof
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frbrgroupidcdi_FETCH-LOGICAL-1942t-2c4cacf2dad59e78577d3d7f8f58c935f8a8c2afdd8add5811d56c439c2b7e6d3
rsrctypearticles
prefilterarticles
languageeng
creationdate2011
topic
0Adult
1Aged
2Azetidines
3Azetidines - administration & dosage
4Basic Medicine
5Biological and medical sciences
6Blind Method
7Cardiovascular Diseases
8Cardiovascular Diseases - prevention & control
9CARDIOVASCULAR EVENTS
10Cholesterol
11Cholesterol, LDL - analysis
12Cholesterol, LDL - drug effects
13Chronic
14Combination
15Confidence Intervals
16DESIGN
17Diagnosis
18Dose
19Dose-Response Relationship, Drug
20Double
21Double-Blind Method
22Drug
23Drug Administration Schedule
24Drug Therapy
25Drug Therapy, Combination
26EFFICACY
27Ezetimibe
28Farmaceutiska vetenskaper
29FARMACI
30Fast track
31Fast track — Articles
32Female
33Follow
34Follow-Up Studies
35General aspects
36Health aspects
37HEMODIALYSIS
38Humans
39Hypolipidemic Agents
40Hypolipidemic Agents - administration & dosage
41Hypolipidemic Agents - adverse effects
42Internal Medicine
43Kidney diseases
44Kidney Function Tests
45Kidneys
46Low density lipoproteins
47Male
48Medical and Health Sciences
49Medical sciences
50Medicin och hälsovetenskap
51Medicinska och farmaceutiska grundvetenskaper
52METAANALYSIS
53Middle Aged
54Nephrology. Urinary tract diseases
55Nephropathies. Renovascular diseases. Renal failure
56OUTCOMES
57PARTICIPANTS
58Pharmaceutical Sciences
59PHARMACY
60Physiological aspects
61Reference Values
62Renal Dialysis
63Renal Dialysis - methods
64Renal Dialysis - mortality
65Renal failure
66Renal Insufficiency
67Renal Insufficiency, Chronic - diagnosis
68Renal Insufficiency, Chronic - drug therapy
69Renal Insufficiency, Chronic - mortality
70Renal Insufficiency, Chronic - therapy
71REQUIRING PROLONGED OBSERVATION
72Research
73Response Relationship
74Risk Assessment
75SAFETY
76Severity of Illness Index
77Simvastatin
78Simvastatin - administration & dosage
79Simvastatin - adverse effects
80Survival Analysis
81Time Factors
82Treatment Outcome
83UMCG Approved
84UNITED-KINGDOM HEART
85Up Studies
86Urinary system involvement in other diseases. Miscellaneous
toplevel
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1online_resources
creatorcontrib
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
50on behalf of the SHARP Investigators
51SHARP Investigators
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3NARCIS: Datasets
4NARCIS:Publications
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8MEDLINE (Ovid)
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jtitleThe Lancet (British edition)
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fulltextfulltext
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au
0Baigent, Colin, Prof
1Landray, Martin J, FRCP
2Reith, Christina, MRCP
3Emberson, Jonathan, PhD
4Wheeler, David C, FRCP
5Tomson, Charles, DM
6Wanner, Christoph, Prof
7Krane, Vera, MD
8Cass, Alan, Prof
9Craig, Jonathan, Prof
10Neal, Bruce, Prof
11Jiang, Lixin, MD
12Hooi, Lai Seong, FRCP
13Levin, Adeera, Prof
14Agodoa, Lawrence, Prof
15Gaziano, Mike, Prof
16Kasiske, Bertram, Prof
17Walker, Robert, Prof
18Massy, Ziad A, Prof
19Feldt-Rasmussen, Bo, Prof
20Krairittichai, Udom, MD
21Ophascharoensuk, Vuddidhej, MD
22Fellström, Bengt, Prof
23Holdaas, Hallvard, MD
24Tesar, Vladimir, Prof
25Wiecek, Andrzej, Prof
26Grobbee, Diederick, Prof
27de Zeeuw, Dick, Prof
28Grönhagen-Riska, Carola, Prof
29Dasgupta, Tanaji, MRCP
30Lewis, David, MRCP
31Herrington, William, MRCP
32Mafham, Marion, MD
33Majoni, William, FRACP
34Wallendszus, Karl, MSc
35Grimm, Richard, Prof
36Pedersen, Terje, Prof
37Tobert, Jonathan, PhD
38Armitage, Jane, Prof
39Baxter, Alex, BA
40Bray, Christopher, PhD
41Chen, Yiping, DPhil
42Chen, Zhengming, Prof
43Hill, Michael, DPhil
44Knott, Carol, MSc
45Parish, Sarah, DPhil
46Simpson, David
47Sleight, Peter, Prof
48Young, Alan, DPhil
49Collins, Rory, Prof
aucorp
0on behalf of the SHARP Investigators
1SHARP Investigators
formatjournal
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ristypeJOUR
atitleThe effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
jtitleThe Lancet (British edition)
addtitleLancet
date2011
risdate2011
volume377
issue9784
spage2181
epage2192
pages2181-2192
issn
00140-6736
11474-547X
eissn1474-547X
codenLANCAO
notesCollaborators listed in the online webappendix
abstractSummary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov , NCT00125593 , and ISRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.
copKidlington
pubElsevier Ltd
pmid21663949
doi10.1016/S0140-6736(11)60739-3
oafree_for_read